chr9-107322003-A-G

Variant names:

• chr9-107322003-A-G
• rs377517847
• NM_002874.5:c.702A>G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002874.5(RAD23B):​c.702A>G​(p.Glu234Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RAD23B NM_002874.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257

Genes affected

RAD23B (HGNC:9813): (RAD23 homolog B, nucleotide excision repair protein) The protein encoded by this gene is one of two human homologs of Saccharomyces cerevisiae Rad23, a protein involved in the nucleotide excision repair (NER). This protein was found to be a component of the protein complex that specifically complements the NER defect of xeroderma pigmentosum group C (XP-c) cell extracts in vitro. This protein was also shown to interact with, and elevate the nucleotide excision activity of 3-methyladenine-DNA glycosylase (MPG), which suggested a role in DNA damage recognition in base excision repair. This protein contains an N-terminal ubiquitin-like domain, which was reported to interact with 26S proteasome, and thus this protein may be involved in the ubiquitin mediated proteolytic pathway in cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=-0.257 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD23B	NM_002874.5	c.702A>G	p.Glu234Glu	synonymous_variant	Exon 7 of 10	ENST00000358015.8	NP_002865.1
RAD23B	NM_001244713.1	c.639A>G	p.Glu213Glu	synonymous_variant	Exon 7 of 10		NP_001231642.1
RAD23B	NM_001244724.2	c.486A>G	p.Glu162Glu	synonymous_variant	Exon 7 of 10		NP_001231653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD23B	ENST00000358015.8	c.702A>G	p.Glu234Glu	synonymous_variant	Exon 7 of 10	1	NM_002874.5	ENSP00000350708.3
RAD23B	ENST00000416373.6	c.486A>G	p.Glu162Glu	synonymous_variant	Exon 7 of 10	1		ENSP00000405623.2
RAD23B	ENST00000457811.1	c.288+3124A>G		intron_variant	Intron 3 of 3	3		ENSP00000396975.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.0
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs377517847; hg19: chr9-110084284;